We examined the production of prostanoids and the expression of cyclooxygenase-2 (COX-2) in cultured arterial smooth muscle cells (SMCs) derived from patients with moyamoya disease. Twelve moyamoya and eight control cell strains were examined. The steady-state levels of prostanoids in the culture medium did not differ between moyamoya and control SMCs. When the cells were stimulated by interleukin-1β (IL-1β), prostaglandin EィイD22ィエD2 (PGEィイD22ィエD2) release into the medium was significantly greater from moyamoya SMCs than from control SMCs, while the amounts of prostacyclin and thromboxane B2 did not differ. IL-1β-induced PGEィイD22ィエD2 production by moyamoya SMCs was completely blocked by the addition of indomethacin or NS-398. IL-1β significantly stimulated cell migration and DNA synthesis in control SMCs, but had an inhibitory effect on moyamoya SMCs. The inhibitory effects on the growth and migration of moyamoya SMCs were caused by excessive secretion of PGEィイD22ィエD2 and was reversed by indomethacin treatment. Immunofluorescence studies and Western blot analysis showed greater amounts of COX-2 protein expression in IL-1β-stimulated moyamoya SMCs. These findings suggest that moyamoya SMCs respond to inflammatory stimuli to produce excess amounts of PGEィイD22ィエD2 through the activation of COX-2, which increases vascular permeability and decreases vascular tone. This facilitates the exposure of vessels to blood constituents and promotes the development of intimal thickening in moyamoya disease.